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The handbook is divided in the following chapters: 1. The Entrepreneurial Discovery Process cycle: from priority selection to strategy implementation. The chapter aims at taking stock of the lessons learnt about the EDP so far. What are the conditions for an effective and efficient discovery process? How can we make the process sustainable in time and how to use it to narrow down broad priorities? 2. Good Governance: principles and challenges This chapter explores the governance arrangements needed to ensure that a wide variety of stakeholders participates in the strategies, in particular the business community, and ways to avoid the process being captured/hijacked by interest groups. 3. From Priorities to Projects: selection criteria and selection process Priorities are especially important in smart specialisation strategies, but the other side of the coin is far from trivial: defining projects and calls within priorities areas in a way that allows to best realize the innovation potential of those areas. 4. Transnational cooperation and value chains This chapter reviews experience acquired with regard to the European value-chain approach and EU macro-regions and provides a selected number of examples. 5. Monitoring The chapter draws on experience accumulated so far and clarifies the role of monitoring, the type of monitoring activities and indicators to be used in S3, and provides indicative initiatives developed in various regions.